The discovery of Helicobacter pylori (H. pylori) infection has greatly changed our understanding of upper G.I. tract, diseases, including peptic ulcer disease and stomach cancer. Antibiotics are first-line treatment for ulcer patients which are infected with this bacterium. Also, the World Health Organization has classified H. pylori as a group I or definite carcinogen. People infected with H. pylori have a 3 to 6 fold higher risk of developing gastric cancer than non-infected persons. Progression from superficial gastritis caused by H. pylori to atrophic gastritis with intestinal metaplasia is felt to be a precursor to gastric cancer development. Investigators have postulated that the natural progression of H. pylori-associated chronic gastritis is to atrophic gastritis, which may be prolonged or shortened by dietary factors. A diet rich in fruits and vegetables and low in starch and salt is associated with a decreased risk of developing gastric cancer. The presence of antioxidants in this diet has been postulate to be responsible for the decrease in cancer risk. We postulate that H. pylori increases the susceptibility of gastric cells to injury from reactive oxygen species, in part by generating the production of intracellular reactive oxygen species. The specific aims of this grant are to (1) determine the ability of H. pylori exposure (live bacteria vs. bacterial proteins) to induce related DNA damage in gastric epithelial cell lines; and elucidate the spectrum and repair course of oxidant related DNA adducts formed after exposure to H. pylori. (2) identify the types of reactive oxygen species that are generated by exposure to H. pylori (live bacteria vs. bacterial proteins) using fluorescent microscopy, fluorometer and lucigenin- and luminol-derived chemiluminescence, and determine whether or not cytochrome p450s and/or mitochondria are important in the generation of reactive oxygen species after exposure to H. pylori. (3) Further evaluate the role of glutathione peroxidase and catalase in the detoxification of intracellular reactive oxygen species, and their association with oxidant induced DNA adducts and cell injury. These studies will demonstrate the potential significant role for bacteria in stimulating oxidative cell injury and DNA damage which may increase the susceptibility of lining epithelial cells to carcinogenic conversion.